2022 Fiscal Year Final Research Report
Circulating monocytes in contributing to myocardial involvement of systemic sclerosis
Project/Area Number |
20K08812
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 54020:Connective tissue disease and allergy-related
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Research Institution | Nippon Medical School |
Principal Investigator |
Kuwana Masataka 日本医科大学, 大学院医学研究科, 大学院教授 (50245479)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Keywords | 全身性強皮症 / バイオインフォマティクス / 心筋 |
Outline of Final Research Achievements |
The heart involvement in systemic sclerosis (SSc) is a poor prognostic factor, although the detailed pathogenesis remains unclear. We conducted transcriptomic analysis of myocardial tissue samples obtained by endomyocardial biopsy from SSc patients with primary heart involvement. Compared to the control group (dilated cardiomyopathy), the SSc myocardium showed activation of pathways related to myocardial energy metabolism, such as fatty acid beta-oxidation and the citric acid cycle, and upstream regulators including NUPR1 and IL-1β were predicted to be activated, leading to dysregulation of microtubules and cytoskeleton of the heart. Estimation of immune cell population did not show any significant differences in the number of specific cell types or oligoclonality compared with the control. These findings suggests that SSc myocardium have a distinct molecular pathogenesis compared to dilated cardiomyopathy.
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Free Research Field |
膠原病
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Academic Significance and Societal Importance of the Research Achievements |
本研究はSSc患者心筋を用いた初めてのトランスクリプトーム解析である。症例数が少ない、対照が健常心筋ではなく拡張型心筋症患者の心筋であるなど制約があるものの、仮説なしの網羅的解析により病態と関連するパスウェイや上流制御因子が同定された学術的意義は大きい。本研究成果は難治性病態の解明に役立つとともに、新たに同定された治療標的に対する新規治療薬の開発につながる可能性を秘めている。
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